Key priorities for Australian infection control : summary of findings from the launch of the Centre for Research Excellence in Reducing Healthcare Associated Infections

The launch of the Centre of Research Excellence in Reducing Healthcare Associated Infection (CRE-RHAI) took place in Sydney on Friday 12 October 2012. The mission of the CRE-RHAI is to generate new knowledge about strategies to reduce healthcare associated infections and to provide data on the cost-effectiveness of infection control programs. As well as launching the CRE-RHAI, an important part of this event was a stakeholder Consultation Workshop, which brought together several experts in the Australian infection control community. The aims of this workshop were to establish the research and clinical priorities in Australian infection control, assess the importance of various multi-resistant organisms, and to gather information about decision making in infection control. We present here a summary and discussion of the responses we received.

Intra-amniotic ureaplasma infection : adverse outcomes vary depending on gestation

Background: Ureaplasmas are the most prevalent bacteria isolated from preterm deliveries and the prognosis for neonates varies depending on the gestation at delivery. Ureaplasmas vary their surface-exposed antigen (MBA, a virulence mechanism) during chronic intra-amniotic infections, but it is not known when changes first occur during gestation. Method: U. parvum serovar 3 (2x10e7CFU) was injected intra-amniotically (IA) into six experimental cohorts of pregnant ewes (of n=7), 3 days (d) or 7d before delivery at either: 100d, 124d or 140d gestation (term=145d). Control ewes received IA 10B broth. Fetuses were delivered surgically and ureaplasmas cultured from amniotic fluid (AF), chorioamnion, fetal lung (FL) and umbilical cord. Ureaplasmas were tested by western blot to demonstrate MBA variation. Results: The highest number of ureaplasmas were recovered from FL at 100d gestation after 3 days of infection (p<0.03). Six of 7(86%) 100d–3d FL demonstrated an ureaplasma MBA variant, but only 17% and 15% of FL showed an MBA variant after 3d infection at 124d and 140d gestation respectively. Greatest variation of the MBA occurred in AF and FL at 124d gestation after 7d infection. The least MBA variation was observed at 140d; however, at this time the most severe histological chorioamnionitis was observed. Conclusions: After intra-amniotic ureaplasma injections, higher numbers of ureaplasmas gained access to the FL at 100d gestation than observed at later gestations. This may exacerbate the adverse outcomes for neonates delivered early in gestation. In late gestation, ureaplasma MBA variation was minimal, but chorioamnionitis was the most severe. Adverse pregnancy outcomes associated with IA ureaplasma infection may vary depending on the duration of gestation, the number of ureaplasmas isolated from the fetal tissues and the degree of MBA variation.

Implementation Guide for Surveillance of Clostridium Difficile Infection -- [Consultation Edition]

The Implementation Guide for hospital surveillance of Clostridium difficile infection (CDI) has been produced by the Healthcare Associated Infection (HAI) Technical Working Group of the Australian Commission on Safety and Quality in Health Care (ACSQHC), and endorsed by the HAI Advisory Group. State jurisdictions and the ACSQHC have representatives on the Technical Working Group, and have had input into this document. (See acknowledgements on inside front cover)...

Implementation Guide for Surveillance of Central Line Associated Bloodstream Infection -- [Consultation Edition]

The implementation guide for the surveillance of CLABSI in intensive care units (ICU) was produced by the Healthcare Associated Infection (HAI) Technical Working Group of the Australian Commission on Safety and Quality in Health Care(ACSQHC), and endorsed by the ACSQHC HAI Advisory Committee. State surveillance units, the ACSQHC and the Australian and New Zealand Intensive Care Society (ANZICS) have representatives on the Technical Working Group, and have provided input into this document.

Markers of cutaneous human papillomavirus infection in individuals with tumor-free skin, actinic keratoses, and squamous cell carcinoma

Separately, actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC) have been associated with cutaneous human papillomavirus (HPV) infections. To further explore the association between HPV infection and SCC development, we determined markers of cutaneous HPV infection within a single population in persons with precursor lesions (AK), cancerous lesions (SCC), and without. Serum and plucked eyebrow hairs were collected from 57 tumor-free controls, 126 AK, and 64 SCC cases. Presence of HPV L1 and E6 seroreactivity and viral DNA were determined for HPV types 5, 8, 15, 16, 20, 24, and 38. Significant positive associations with increasing severity of the lesions (controls, AK, and SCC, respectively) were observed for overall HPV L1 seropositivity (13%, 26%, and 37%) and for HPV8 (4%, 17%, and 30%). In parallel, the proportion of L1 seropositive individuals against multiple HPV types increased from 14% to 39% and 45%. The overall E6 seroreactivity, however, tended to decline with AK and SCC, especially for HPV8 (21%, 11%, and 2%). HPV DNA positivity was most prevalent in the AK cases (54%) compared with the SCC cases (44%) and the tumor-free controls (40%). Among all participants, there was a positive trend between overall HPV DNA positivity and L1 seropositivity, but not E6 seropositivity. Taken together, our data suggest that cutaneous HPV infections accompanied by detectable HPV DNA in eyebrow hairs and HPV L1 seropositivity, but not E6 seropositivity, are associated with an increased risk of AK and SCC.

Re: Human papillomavirus infection and incidence of squamous cell and basal cell carcinomas of the skin

Human papillomaviruses (HPVs) cause cervical cancer and some other types of epithelial cancers. HPV types from the phylogenic beta genus (beta-PVs), formerly known as epidermodysplasia verruciformis–associated HPV types, are frequently detected in nonmelanoma skin cancers, especially in squamous cell carcinomas (SCCs). An etiologic relationship with beta-PV infection is suspected...

Mycobacterium abscessus infection and potable water

Mycobacterium abscessus is a rapidly growing mycobacteria responsible for progressive pulmonary disease, soft tissue and wound infections, and can contaminate clinical specimens. Nontuberculous mycobacteria (NTM) are generally considered environmental organisms though M. abscessus has not featured frequently in environmental studies, particularly those examining potable water. In a study of Brisbane potable water, M. abscessus was isolate from ten different locations. The incidence of disease due to M. abscessus has been increasing in Queensland. Aim: To compare genotypically the M. abscessus isolates obtained from water to those obtained from human clinical specimens. Methods: From a study of Brisbane potable water between 2007 and 2009, ten isolates confirmed as M. abscessus were recovered. In addition, one strain was isolated from a rainwater tank of a patient with disease due to M. avium, and another from the swimming pool of a patient with M. intracellulare disease. A random sample of 74 clinical isolates referred to the QLD Mycobacterial reference laboratory during the same time period was available for comparison using repPCR strain typing (Diversilab). Results: The drinking water isolates formed two distinct strain patterns (A and B) that shared >90% similarity. The tankwater isolate (pattern C) shared >85% similarity with the potable water isolates, but the pool isolate (D) was distinctly different. Fifty-three clinical isolates clustered tightly (>95% similarity) with the Group A potable water isolates, 4 patients with Group B. Thirteen patient isolates clustered with the Rainwater tank isolate. One patient matched the pool isolate. There were a further 3 patient isolates that were unrelated to the water isolates. No differences were found between strain types in terms of geographic origin, gender, age, or site/type of infection. Conclusion: The high degree of similarity between strains of M. abscessus from potable water and strains causing infection in humans from the same area, strengthens the possibility that drinking water may be a source of infection in these patients.

Ureaplasma parvum serovar 3 multiple banded antigen size variation after chronic intra-amniotic infection/colonization

Ureaplasma species are the microorganisms most frequently associated with adverse pregnancy outcomes. The multiple banded antigen (MBA), a surface-exposed lipoprotein, is a key virulence factor of ureaplasmas. The MBA demonstrates size variation, which we have shown previously to be correlated with the severity of chorioamnion inflammation. We aimed to investigate U. parvum serovar 3 pathogenesis in vivo, using a sheep model, by investigating: MBA variation after long term (chronic) and short term (acute) durations of in utero ureaplasma infections, and the severity of chorioamnionitis and inflammation in other fetal tissues. Inocula of 2x107 colony-forming-units (CFU) of U. parvum serovar 3 (Up) or media controls (C) were injected intra-amniotically into pregnant ewes at one of three time points: day 55 (69d Up, n=8; C69, n=4); day 117 (7d Up, n=8; C7, n=2); and day 121 (3d Up, n=8; C3, n=2) of gestation (term=145-150d). At day 124, preterm fetuses were delivered surgically. Samples of chorioamnion, fetal lung, and umbilical cord were: (i) snap frozen for subsequent ureaplasma culture, and (ii) fixed, embedded, sectioned and stained by haematoxylin and eosin stain for histological analysis. Selected fetal lung clinical ureaplasma isolates were cloned and filtered to obtain cultures from a single CFU. Passage 1 and clone 2 ureaplasma cultures were tested by western blot to demonstrate MBA variation. In acute durations of ureaplasma infection no MBA variants (3d Up) or very few MBA variants (7d Up) were present when compared to the original inoculum. However, numerous MBA size variants were generated in vivo (alike within contiguous tissues, amniotic fluid and fetal lung, but different variants were present within chorioamnion), during chronic, 69d exposure to ureaplasma infection. For the first time we have shown that the degree of ureaplasma MBA variation in vivo increased with the duration of gestation.

Mid-gestation intra-amniotic infection with Ureaplasma parvum is resolved within spiny mice (Acomys cahirinus) by term delivery: but caused chronic infection of fetal lungs and placentae

Background: Ureaplasma species in amniotic fluid at the time of second-trimester amniocentesis increases the risk of preterm birth, but most affected pregnancies continue to term (Gerber et al. J Infect Dis 2003). We aimed to model intra-amniotic (IA) ureaplasma infection in spiny mice, a species with a relatively long gestation (39 days) that allows investigation of the disposition and possible clearance of ureaplasmas in the feto-placental compartment. Method: Pregnant spiny mice received IA injections of U. parvum serovar 6 (10µL, 1x104 colony-forming-units in PBS) or 10B media (10µL; control) at 20 days (d) of gestation (term=39d). At 37d fetuses (n=3 ureaplasma, n=4 control) were surgically delivered and tissues were collected for; bacterial culture, ureaplasma mba and urease gene expression by PCR, tissue WBC counts and indirect fluorescent antibody (IFA) staining using anti-ureaplasma serovar 6 (rabbit) antiserum. Maternal and fetal plasma IgG was measured by Western blot. Results: Ureaplasmas were not detected by culture or PCR in fetal or maternal tissues but were visualized by IFA within placental and fetal lung tissues, in association with inflammatory changes and elevated WBC counts (p<0.0001). Anti-ureaplasma IgG was detected in maternal (2/2 tested) and fetal (1/2 tested) plasma but not in controls (0/3). Conclusions: IA injection of ureaplasmas in mid-gestation spiny mice caused persistent fetal lung and placental infection even though ureaplasmas were undetectable using standard culture or PCR techniques. This is consistent with resolution of IA infection, which may occur in human pregnancies that continue to term despite detection of ureaplasmas in mid-gestation.

Surgical site infection prevention following total hip arthroplasty in Australia : a cost-effectiveness analysis

Background: Surgical site infection (SSI) is associated with substantial costs for health services, reduced quality of life, and functional outcomes. The aim of this study was to evaluate the cost-effectiveness of strategies claiming to reduce the risk of SSI in hip arthroplasty in Australia. Methods: Baseline use of antibiotic prophylaxis (AP) was compared with no antibiotic prophylaxis (no AP), antibiotic-impregnated cement (AP þ ABC), and laminar air operating rooms (AP þ LOR). A Markov model was used to simulate long-term health and cost outcomes of a hypothetical cohort of 30,000 total hip arthroplasty patients from a health services perspective. Model parameters were informed by the best available evidence. Uncertainty was explored in probabilistic sensitivity and scenario analyses. Results: Stopping the routine use of AP resulted in over Australian dollars (AUD) $1.5 million extra costs and a loss of 163 quality-adjusted life years (QALYs). Using antibiotic cement in addition to AP (AP þ ABC)generated an extra 32 QALYs while saving over AUD $123,000. The use of laminar air operating rooms combined with routine AP (AP þ LOR) resulted in an AUD $4.59 million cost increase and 127 QALYs lost compared with the baseline comparator. Conclusion: Preventing deep SSI with antibiotic prophylaxis and antibiotic-impregnated cement has shown to improve health outcomes among hospitalized patients, save lives, and enhance resource allocation. Based on this evidence, the use of laminar air operating rooms is not recommended.

Impact of Wolbachia on infection with chikungunya and yellow fever viruses in the mosquito vector Aedes aegypti

Incidence of disease due to dengue (DENV), chikungunya (CHIKV) and yellow fever (YFV) viruses is increasing in many parts of the world. The viruses are primarily transmitted by Aedes aegypti, a highly domesticated mosquito species that is notoriously difficult to control. When transinfected into Ae. aegypti, the intracellular bacterium Wolbachia has recently been shown to inhibit replication of DENVs, CHIKV, malaria parasites and filarial nematodes, providing a potentially powerful biocontrol strategy for human pathogens. Because the extent of pathogen reduction can be influenced by the strain of bacterium, we examined whether the wMel strain of Wolbachia influenced CHIKV and YFV infection in Ae. aegypti. Following exposure to viremic blood meals, CHIKV infection and dissemination rates were significantly reduced in mosquitoes with the wMel strain of Wolbachia compared to Wolbachia-uninfected controls. However, similar rates of infection and dissemination were observed in wMel infected and non-infected Ae. aegypti when intrathoracic inoculation was used to deliver virus. YFV infection, dissemination and replication were similar in wMel-infected and control mosquitoes following intrathoracic inoculations. In contrast, mosquitoes with the wMelPop strain of Wolbachia showed at least a 10(4) times reduction in YFV RNA copies compared to controls. The extent of reduction in virus infection depended on Wolbachia strain, titer and strain of the virus, and mode of exposure. Although originally proposed for dengue biocontrol, our results indicate a Wolbachia-based strategy also holds considerable promise for YFV and CHIKV suppression.

Implementation guide for surveillance of Clostridium difficile infection

The Implementation Guide for hospital surveillance of Clostridium difficile infection (CDI) has been produced by the Healthcare Associated Infection (HAI) Technical Working Group of the Australian Commission on Safety and Quality in Health Care (ACSQHC), and endorsed by the HAI Advisory Group. State jurisdictions and the ACSQHC have representatives on the Technical Working Group, and have had input into this document. The Guide is intended to be used by Australian hospitals and organisations to support the implementation of hospital-identified Clostridium difficile infection (CDI) surveillance using the endorsed case definition in this guide. It has been produced to support consistency of surveillance activities and is not intended to replace clinical assessment of infection for patient management.

Wolbachia infection alters olfactory-cued locomotion in Drosophila spp

Wolbachia pipientis is an endosymbiotic bacterium present in diverse insect species. Although it is well studied for its dramatic effects on host reproductive biology, little is known about its effects on other aspects of host biology, despite its presence in a wide array of host tissues. This study examined the effects of three Wolbachia strains on two different Drosophila species, using a laboratory performance assay for insect locomotion in response to olfactory cues. The results demonstrate that Wolbachia infection can have significant effects on host responsiveness that vary with respect to the Wolbachia strain-host species combination. The wRi strain, native to Drosophila simulans, increases the basal activity level of the host insect as well as its responsiveness to food cues. In contrast, the wMel strain and the virulent wMelPop strain, native to Drosophila melanogaster, cause slight decreases in responsiveness to food cues but do not alter basal activity levels in the host. Surprisingly, the virulent wMelPop strain has very little impact on host responsiveness in D. simulans. This novel strain-host relationship was artificially created previously by transinfection. These findings have implications for understanding the evolution and spread of Wolbachia infections in wild populations and for Wolbachia-based vector-borne disease control strategies currently being developed.

Humans, ‘things’ and space : costing hospital infection control interventions

Background: Previous attempts at costing infection control programmes have tended to focus on accounting costs rather than economic costs. For studies using economic costs, estimates tend to be quite crude and probably underestimate the true cost. One of the largest costs of any intervention is staff time, but this cost is difficult to quantify and has been largely ignored in previous attempts. Aim: To design and evaluate the costs of hospital-based infection control interventions or programmes. This article also discusses several issues to consider when costing interventions, and suggests strategies for overcoming these issues. Methods: Previous literature and techniques in both health economics and psychology are reviewed and synthesized. Findings: This article provides a set of generic, transferable costing guidelines. Key principles such as definition of study scope and focus on large costs, as well as pitfalls (e.g. overconfidence and uncertainty), are discussed. Conclusion: These new guidelines can be used by hospital staff and other researchers to cost their infection control programmes and interventions more accurately.